Infection

, Volume 41, Issue 2, pp 361–370

Previous outpatient antibiotic use in patients admitted to hospital for COPD exacerbations: room for improvement

Authors

    • Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Ciber de Enfermedades Respiratorias (CIBERES)Hospital Clinic
    • Servei de PneumologiaHospital Clinic
  • J. J. Soler-Cataluña
    • Pneumology Unit, Internal Medicine ServiceHospital de Requena
  • F. Baranda
    • Department of PneumologyHospital Universitario Cruces
  • P. Cordero
    • Department of PneumologyHospital Nisa 9 de Octubre
  • J.-V. Greses
    • Department of PneumologyHospital Nisa 9 de Octubre
  • C. de la Roza
    • Medical DepartmentBayer Hispania
Clinical and Epidemiological Study

DOI: 10.1007/s15010-012-0316-8

Cite this article as:
Miravitlles, M., Soler-Cataluña, J.J., Baranda, F. et al. Infection (2013) 41: 361. doi:10.1007/s15010-012-0316-8

Abstract

Purpose

Several studies have analyzed factors associated to hospitalization in chronic obstructive pulmonary disease (COPD) patients. However, data are lacking on the quality of treatment received by patients prior to hospital admission. The present study analyzed how often patients requiring hospitalization for a COPD exacerbation had received previous treatment for the exacerbation, particularly antibiotics.

Methods

This was a multicenter, cross-sectional, observational study conducted in 30 Spanish hospitals among COPD patients aged >40 years who were hospitalized for an acute exacerbation. Patients were grouped according to whether or not they had received treatment prior to admission and, subsequently, according to whether or not they had received antibiotics. Patient eligibility for antibiotic therapy was assessed using both national and European guidelines.

Results

The study population consisted of 298 patients, of which 277 (93 %) were men, with a mean [standard deviation (SD)] age of 69.1 (9.5) years. One hundred and thirty-three patients (45 %) had received treatment prior to admission; among these, 76/133 (57 %) had received antibiotic therapy. However, 81–91 % of these patients fulfilled criteria for this therapy. Antibiotic use was significantly associated with yellow or green–yellow sputum prior to the exacerbation, a higher number of exacerbations in the previous year, more visits to emergency departments, and bronchiectasis. On the other hand, 10–20 % of patients who did receive antibiotics were not eligible for this therapy according to guidelines.

Conclusions

This study demonstrates a low rate of previous outpatient treatment and antibiotic use among patients with a COPD exacerbation requiring hospital admission.

Keywords

COPDAntibioticsHospitalizationExacerbation

Introduction

Chronic obstructive pulmonary disease (COPD) is one of the most important causes of death and disability in developed countries, with important social and economic repercussions. The poor quality of life of COPD patients may be further impacted by recurrent periods of worsening of symptoms or acute exacerbations [1], which occur, on average, once or twice a year [2]. COPD exacerbations often require medical intervention and are the main cause of hospital admission and death among these patients [3, 4]. Exacerbations of COPD account for nearly 10 % of all medical admissions [5], and patients with severe COPD are at higher risk for suffering more severe exacerbations requiring hospitalization [6].

Hospitalizations negatively impact on patients’ quality of life [3] and increase the risk of readmission [7] and the risk of death, independently of the severity of the disease [6], the number of previous admissions [6], and other classical prognostic factors [8]. Hospitalizations also increase the economic burden of the disease, representing 40.4 % of total healthcare costs in patients with mild COPD, and increasing up to 62.6 % in patients with severe COPD [9]. It has also been estimated that hospitalizations account for nearly 60 % of the total cost of COPD exacerbations [10].

Several studies have focused on potentially modifiable risk factors associated with hospital admission [11], which can be used to develop targeted interventions aimed at admission reduction. Early recognition of symptoms and prompt treatment have been shown to have an important effect on recovery and on the need for hospitalization [12]; however, data are lacking on the quality of treatment received by patients prior to hospital admission. Bacterial infections are one of the most frequent etiologies of acute exacerbations [13], and antibiotics are an important component of exacerbation treatment [14]. Antibiotic therapy is usually chosen based on empirical evidence and guided by Anthonisen’s criteria of bacterial involvement [15]. Optimal antibiotic selection should be based on risk factors for poor outcome [16]. Despite these recommendations, patients presenting to their caregivers with symptoms conforming to antibiotic treatment criteria do not always receive antibiotic treatment [17, 18], a factor which might have important repercussions on the risk of admission.

The present study was designed to analyze how often patients requiring hospitalization for a COPD exacerbation had received previous treatment for the exacerbation, particularly antibiotics. Secondary objectives included assessing: (1) the relationship between the patient’s condition and the probability of receiving treatment, and (2) how many patients fulfilling criteria for antibiotic therapy according to COPD management guidelines [19, 20] did not receive outpatient antibiotic treatment prior to admission.

Methods

Study design and patients

This was a multicenter, cross-sectional, observational study conducted in 30 Spanish hospitals from June 2010 to March 2011. The included patients were those aged >40 years with a diagnosis of COPD, who required hospitalization for an acute exacerbation. COPD diagnosis was confirmed by spirometry performed in stable state in the last 12 months showing an FEV1/FVC post-bronchodilator <0.7, and a smoking history of at least 10 pack-years. Exacerbation was defined and classified according to Anthonisen’s criteria [15]. Exclusion criteria included hospitalization for a cause other than a COPD exacerbation (pneumonia, thromboembolism, cardiac insufficiency, pneumothorax, etc.), a lack of clinical history data, or participation in a clinical trial in the previous 2 months. The study was approved by the Ethics Committee of the Hospital Clinic (Barcelona, Spain) and all participants provided written informed consent.

The following patient data were recorded: socio-demographic and anthropometric data (age, sex, height, weight); clinical data (self-reported smoking habit, medical conditions and baseline COPD characteristics, stable COPD treatment and vaccines, number and characteristics of previous COPD exacerbations, and where the treatment was received); and data regarding the exacerbation leading to the current hospital admission (symptoms, previous treatment including antibiotic therapy in the last 2 weeks, and who prescribed the antibiotic). Patients were grouped according to whether they did or did not receive treatment prior to admission, and subdivided into those receiving antibiotics and those receiving treatment without antibiotics.

Eligibility for antibiotic therapy among admitted patients was assessed according to the Spanish Thoracic Society (SEPAR) [19] COPD exacerbation treatment guidelines (Criterion A). These guidelines specify that an antibiotic is recommended in patients presenting changes in their sputum (purulence and/or volume), i.e., Anthonisen’s type 1 (increased dyspnea, sputum volume, and sputum purulence) and type 2 (two of the three clinical findings). For comparison, the more restrictive criteria of the European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases (ERS/ESCMID) guidelines [20] were also applied (Criterion B), which recommend antibiotics only when sputum purulence is present (i.e., type 1, and type 2 only when purulence is present).

Statistical analysis

Percentages (absolute or relative) were used to describe categorical variables. Quantitative variables were expressed as mean scores ± standard deviation (SD). Categorical variables were compared using a χ2 test (Fisher’s exact test), and mean values of quantitative variables were compared using the Student’s t-test. In cases of statistically significant differences, the Mann–Whitney U-test was used for specific comparisons. Statistical analyses were performed using the SPSS v.17.0 statistical software package (SPSS Inc., Chicago, IL, USA). Statistical significance was set at p < 0.05.

Results

Patient characteristics

Three hundred and one patients were recruited, of whom three were ineligible, as they did not meet all the inclusion criteria (one had no spirometric confirmation of COPD and two lacked information regarding admission). The study population consisted of 298 individuals admitted to hospital due to a COPD exacerbation, of which 277 (93 %) were men, with a mean (SD) age of 69.1 (9.5) years. Sociodemographic, anthropometric, and clinical characteristics of patients, including COPD characterization and treatment, are described in Table 1. Patients presented a mean body mass index (BMI) of 27.6 (4.7) kg/m2, and 82 (28 %) were current smokers. The mean FEV1 [% predicted (SD)] was 44.3 % (15.2 %), reflecting the high number of patients with severe [n = 135 (45.3 %)] or very severe COPD [n = 57 (19.1 %)]. All patients were receiving treatment for their stable COPD; inhaled corticoids (94 %) and long-acting beta2 agonists (90 %), alone or in combination, were the most frequently used treatments. Three out of four patients had received the seasonal influenza vaccine, and one out of four had received the pneumococcal vaccine. Patients experienced a mean of 1.6 (2.0) exacerbations in the previous year, with 109 (34.9 %) patients reporting ≥2 exacerbations. Nearly 11 % of patients presented four or more exacerbations requiring antibiotic therapy in the previous year. Ninety-nine (33 %) patients had visited a general practitioner, and 65 (22 %) had attended at least one emergency department in the previous year due to a COPD exacerbation. One out of three patients had been admitted to hospital for a COPD exacerbation in the last year.
Table 1

Patient characteristics

Characteristics

Total patients, n

298

Age, years ± SD

69.2 ± 9.5

Sex, n (%)

 Male

277 (93.0)

BMI, kg/m2 ± SD

27.6 ± 4.7

Smoking status, n (%)

 Smoker

82 (27.5)

 Ex-smoker

216 (72.5)

Smoking history, pack-years ± SD

51.4 ± 23.6

Most frequent comorbidities, n (%)

 Hypertension

132 (44.3)

 Diabetesa

65 (21.8)

 Cardiopathyb

82 (27.6)

 Neurologic disease

18 (6.0)

 Other pulmonary chronic diseases

83 (37.2)

 Digestive diseases

75 (25.2)

 Renal diseases

13 (4.4)

 Neoplasms

23 (7.7)

 Anxiety/depression

54 (18.1)

 Previous pneumonia

34 (11.5)

COPD symptoms in stable phasec, n (%)

 Dyspnea grade 0

7 (2.3)

 Dyspnea grade 1

44 (14.8)

 Dyspnea grade 2

130 (43.6)

 Dyspnea grade 3

73 (24.5)

 Dyspnea grade 4

26 (8.7)

 Chronic cough

178 (59.7)

 Sputum production

157 (52.7)

  White

124 (41.6)

  Yellow or green-yellow

32 (10.8)

Pseudomonas isolation in the last year, n (%)

23 (7.7)

Post-bronchodilator spirometry, ± SD

 FVC, % predicted

68.3 ± 16.7

 FEV1, % predicted

44.3 ± 15.2

 FEV1/FVC

49.3 ± 12.1

COPD classification, n (%)

 Mild

3 (1.0)

 Moderate

103 (34.6)

 Severe

135 (45.3)

 Very severe

57 (19.1)

Stable COPD treatment, n (%)

 Long-acting anticholinergic (tiotropium)

206 (69.1)

 Inhaled corticosteroids

279 (93.6)

 LABA

267 (89.6)

 Xantins

59 (19.8)

 Mucolytics

91 (30.5)

 Oxygen therapy

92 (30.9)

 Noninvasive mechanical ventilation

18 (6.0)

Vaccines, n (%)

 Seasonal influence vaccine

231 (77.5)

 Influence A vaccine

102 (34.2)

 Pneumococcal vaccine

72 (24.2)

Mean no. of exacerbations in the previous year, ± SD

1.6 ± 2.0

Exacerbations in the previous year, n (%)

 0

3 (1.0)

 1

69 (23.2)

 2–3

77 (24.2)

 ≥4

32 (10.7)

Consultations/admissions in the previous year, no. of patients (%)

 Outpatient department (general practitioner)

99 (33.2)

 Emergency

65 (21.8)

 Hospital admission

100 (33.6)

BMI body mass index, LABA long-acting beta2 agonists, SD standard deviation

aIncludes diabetes types I and II, and diabetes with target tissue injury

bIncludes ischemic cardiopathy, arrhythmia, and cardiac insufficiency

cMRC scale [44]

Exacerbation symptoms and treatments

Data regarding the exacerbation leading to the current hospital admission and the treatment received are shown in Table 2. Approximately half of the exacerbations (52 %) were Anthonisen’s type 1 and 30 % were type 2. One hundred and thirty-three patients (45 %) had received treatment prior to admission; among these, 76/133 (57 %) had received antibiotic therapy, mainly prescribed by a general practitioner (63 %), or at an emergency department (21 %) before the current admission (Fig. 1). The mean duration of previous antibiotic therapy before admission was 5.9 days (SD 2.9 days). Most patients in our study [222 (74.4 %)] had not received prior antibiotic therapy. Microbiological sputum tests were performed at admission for 126 (42 %) patients, with Haemophilus influenzae (3 %), Pseudomonas aeruginosa (2.7 %), and Streptococcus pneumoniae (2.3 %) being the most frequent species isolated. Five out of eight patients with P. aeruginosa had a previous isolation of this pathogen in the last year.
Table 2

Exacerbation and treatment data at admission

Parameters

n (%)

Exacerbation symptoms

 Increased dyspnea

285 (95.6)

 Increased cough

260 (87.2)

 Increased sputum production

238 (79.9)

 Sputum purulence

176 (59.1)

 Fever >38 °C

85 (28.5)

Exacerbation type (Anthonisen’s scale)

 Type 1

156 (52.3)

 Type 2

89 (29.9)

 Type 3

53 (17.8)

Received previous treatment for this exacerbation

133 (44.6)

 Antibiotic treatment in the last 2 weeks

76/133 (57.1)

 Increased bronchodilator treatment

92/133 (69.1)

 Oral corticosteroids

48/133 (36.0)

 Introduction of inhaled corticosteroids

7/133 (5.3)

Received antibiotic treatmenta

76 (25.5)

 Levofloxacin

23/76 (30.2)

 Moxifloxacin

22/76 (28.9)

 Amoxicillin–clavulanic acid

13/76 (17.1)

 Azithromycin

7/76 (9.2)

 Cefditoren

5/76 (6.6)

 Cefuroxime

2/76 (2.6)

 Clarithromycin

2/76 (2.6)

 Ciprofloxacin

2/76 (2.6)

 Other

4/76 (5.3)

Prescriber of antibiotic treatmentb

 General practitioner

48 (63.2)

 Emergency practitioner

16 (21.1)

 Pneumologist

7 (9.2)

 Internal medicine specialist

3 (3.9)

 Self-prescribed

1 (1.3)

 Self-management plan/self-care administered to the patient

1 (1.3)

Sputum culture at admission

126 (42.3)

Isolated species

 

 Haemophilus influenzae

9/126 (7.1)

 Pseudomonas aeruginosa

8/126 (6.3)

 Streptococcus pneumoniae

7/126 (5.5)

 Candida albicans

2/126 (1.6)

 Escherichia coli

2/126 (1.6)

 Proteus mirabilis

2/126 (1.6)

 Staphylococcus epidermidis

2/126 (1.6)

 Stenotrophomonas maltophilia

2/126 (1.6)

 Moraxella catarrhalis

1/126 (0.8)

 Serratia

1/126 (0.8)

 Alcaligenes

1/126 (0.8)

 Aspergillus

1/126 (0.8)

aIn four patients, a combination of two antibiotics was administered: amoxicillin + moxifloxacin; levofloxacin + moxifloxacin; clarithromycin + cefditoren; cefuroxime + moxifloxacin

bData available for patients having received antibiotic therapy (n = 76)

https://static-content.springer.com/image/art%3A10.1007%2Fs15010-012-0316-8/MediaObjects/15010_2012_316_Fig1_HTML.gif
Fig. 1

Distribution of patients receiving previous treatment (n = 298) and antibiotic use among those receiving prior treatment (n = 133)

The patient characteristics and exacerbation symptoms by treatment group are shown in Table 3. Sputum purulence and more severe exacerbations (Anthonisen’s type 1) were significantly associated with receiving previous treatment. Other characteristics associated with receiving treatment included higher FEV1/FVC, chronic cough and sputum, more exacerbations in the last year, and more visits to emergency departments due to exacerbations.
Table 3

Patient characteristics and exacerbation symptoms by treatment group (n = 298)

Parameter

Patients without previous treatment (n = 165)

Patients with previous treatment (n = 133)

p-value

Patient characteristics

 Age, years ± SD

70.3 ± 9.7

67.7 ± 9.0

0.22

 Sex, n (%)

  Male

154 (93.3)

123 (92.5)

0.77

 BMI, kg/m2 ± SD

27.4 ± 4.5

27.8 ± 5.0

0.57

 Current smoker, n (%)

40 (24.2)

42 (31.6)

0.16

 Smoking history, pack-years ± SD

50.9 ± 23.3

52.1 ± 24.1

0.66

 Significant comorbiditiesa, n (%)

76 (46.1)

65 (48.9)

0.63

 FVC, % predicted ± SD

68.7 ± 16.6

67.8 ± 16.9

0.77

 FEV1, % predicted ± SD

43.8 ± 14.8

44.9 ± 15.7

0.61

 FEV1/FVC ± SD

48.2 ± 10.7

50.7 ± 13.6

0.044

 COPD symptoms in stable phase, n (%)

  Dyspnea grade

   I

25 (16.4)

19 (14.8)

0.84

   II

72 (47.4)

58 (45.3)

0.82

   III

40 (26.3)

33 (25.8)

0.97

   IV

13 (8.6)

13 (10.2)

0.80

  Chronic cough

79 (48.2)

99 (74.4)

<0.0001

  Sputum

66 (40.0)

91 (68.4)

<0.0001

   White

50 (76.9)

74 (81.3)

0.64

   Yellow or green-yellow

15 (23.1)

17 (18.7)

0.64

 Pseudomonas isolation in the last year, n (%)

14 (8.5)

9 (6.8)

0.08

 No. of exacerbations in the last year ± SD

1.4 ± 2.1

1.8 ± 1.9

0.011

 Hospital admissions in the previous year ± SD

0.9 ± 1.8

0.7 ± 1.5

0.73

 Emergency department visits in the previous year ± SD

0.4 ± 1.2

0.6 ± 1.4

0.003

 Bronchiectasis, n (%)

16 (9.7)

13 (9.8)

0.98

 Previous pneumonia, n (%)

16 (9.8)

18 (13.5)

0.32

Exacerbation symptoms, n (%)

 Increased dyspnea

156 (94.5)

129 (97.0)

0.30

 Increased cough

141 (85.5)

119 (89.5)

0.30

 Sputum

124 (75.2)

114 (85.7)

0.023

 Sputum purulence

67 (40.6)

109 (82.0)

<0.0001

 Fever >38°

42 (25.5)

43 (32.3)

0.19

 Anthonisen’s exacerbation type

  Type 1 (severe)

58 (35.2)

98 (73.7)

<0.0001

  Type 2 (moderate)

66 (40.0)

23 (17.3)

<0.0001

  Type 3 (mild)

41 (24.8)

12 (9.0)

0.001

SD standard deviation

aCardiopathy, diabetes, renal insufficiency, hepatic diseases

Bold values are statistically significant (p < 0.05)

The presence of yellow or green-yellow sputum prior to the exacerbation, a higher number of exacerbations in the previous year, more visits to emergency departments, and bronchiectasis were significantly associated with antibiotic use among patients who received treatment prior to admission (Table 4). There were no significant associations between exacerbation symptoms and previous antibiotic use.
Table 4

Patient characteristics and exacerbation symptoms by antibiotic subgroup among patients receiving treatment (n = 133)

Parameter

Patients not receiving antibiotics (n = 57)

Patients receiving antibiotics (n = 76)

p-value

Patient characteristics

 Age, years ± SD

67.6 ± 8.9

67.8 ± 9.1

0.61

 Sex, n (%)

  Male

53 (93.0)

70 (92.1)

0.85

 BMI, kg/m2 ± SD

27.3 ± 5.5

28.1 ± 4.7

0.56

 Current smoker, n (%)

16 (28.1)

26 (34.2)

0.45

 Smoking history, pack-years ± SD

54.1 ± 27.1

50.6 ± 21.5

0.94

 Significant comorbiditiesa, n (%)

23 (40.4)

42 (55.3)

0.09

 FVC, % predicted

69.1 ± 18.0

66.9 ± 16.1

0.47

 FEV1, % predicted

45.7 ± 16.1

44.2 ± 15.6

0.68

 FEV1/FVC

49.9 ± 13.7

51.3 ± 13.5

0.51

 COPD symptoms in stable phase, n (%)

  Dyspnea grade

   I

7 (13.2)

12 (16.0)

0.85

   II

31 (58.5)

27 (36.0)

0.019

   III

11 (20.8)

22 (29.3)

0.37

   IV

3 (5.7)

10 (13.3)

0.26

  Chronic cough

47 (82.5)

52 (68.4)

0.07

  Sputum

39 (68.4)

52 (68.4)

1.00

   White

37 (94.9)

37 (71.2)

0.009

   Yellow or green-yellow

2 (5.1)

15 (28.9)

0.009

 Pseudomonas isolation in the last year

2 (3.5)

7 (9.2)

0.42

 No. of exacerbations in the last year

1.4 ± 1.7

2.0 ± 1.9

0.041

 Hospital admissions in the previous year

0.7 ± 1.5

0.8 ± 1.5

0.26

 Emergency department visits in the previous year

0.3 ± 0.8

0.8 ± 1.8

0.006

 Bronchiectasis

2 (3.5)

11 (14.5)

0.035

 Previous pneumonia

7 (12.5)

11 (14.5)

0.71

Exacerbation symptoms

 Increased dyspnea

55 (96.5)

74 (97.4)

0.77

 Increased cough

54 (94.7)

65 (85.5)

0.09

 Sputum

50 (87.7)

64 (84.2)

0.57

 Sputum purulence

47 (82.5)

62 (81.6)

0.90

 Fever >38°

19 (33.3)

24 (31.6)

0.830

 Anthonisen exacerbation type

  Type 1

42 (73.7)

56 (73.7)

0.84

  Type 2

11 (19.3)

12 (15.8)

0.77

  Type 3

4 (7.0)

8 (10.5)

0.69

SD standard deviation

aCardiopathy, diabetes, renal insufficiency, hepatic diseases

Bold values are statistically significant (p < 0.05)

Table 5 presents an analysis of eligibility for antibiotic treatment among all patients (Table 5A) and among patients receiving prior treatment (Table 5B). Globally, 245 (82 %) patients fulfilled Criterion A for eligibility for antibiotic treatment, while 175 (58.7 %) fulfilled Criteria A and B (Table 5A). Importantly, 93 % (Criterion A) and 82.4 % (Criterion B) of treated patients who did not receive an antibiotic were eligible for antibiotic treatment according to guidelines (Table 5B). Conversely, among patients taking antibiotics on admission, 89.5 % (Criterion A) and 80.3 % (Criterion B) fulfilled antibiotic recommendation requirements (Table 5B).
Table 5

Eligibility for antibiotic treatment according to Criteria A and B among all patients (n = 298) (A) and patients receiving prior treatment (n = 133) (B) [19, 20]

 

Total (n = 298), n/N (%)

Patients with antibiotic treatment (n = 76), n/N (%)

Patients without antibiotic treatment (n = 222), n/N (%)

(A)

 Criterion A

  Antibiotic recommended

245/298 (82.2)

68/76 (89.5)

177/222 (79.7)

  Antibiotic not recommended

53/298 (17.8)

8/76 (10.5)

45/222 (20.3)

 Criterion B

  Antibiotic recommended

175/298 (58.7)

61/76 (80.3)

114/222 (51.3)

  Antibiotic not recommended

123/298 (41.3)

15/76 (19.7)

108/222 (48.6)

 

Total (n = 133), n/N (%)

Patients with antibiotic treatment (n = 76), n/N (%)

Patients without antibiotic treatment (n = 57), n/N (%)

(B)

 Criterion A

  Antibiotic recommended

121/133 (91.0)

68/76 (89.5)

53/57 (93.0)

  Antibiotic not recommended

12//133 (9.0)

8/76 (10.5)

4/57 (7.0)

 Criterion B

  Antibiotic recommended

108/133 (81.2)

61/76 (80.3)

47/57 (82.4)

  Antibiotic not recommended

25/133 (18.8)

15/76 (19.7)

10/57 (17.5)

Criterion A: type 1 exacerbations (three cardinal symptoms) and type 2 exacerbations (two cardinal symptoms) [19]

Criterion B: type 1 exacerbations (three cardinal symptoms) and type 2 exacerbations (two cardinal symptoms, one being sputum purulence) [20]

Discussion

The results of our study show a low treatment rate (45 %) in the outpatient setting for COPD exacerbation among moderate-to-severe COPD patients who later required hospitalization. Moreover, antibiotic usage was also found to be low, with 74 % of patients not receiving antibiotic therapy, despite the fact that the majority of patients fulfilled national and international guidelines criteria for antibiotic recommendation. Among patients with severe type 1 exacerbations, as many as 35 % did not receive an antibiotic before admission. These findings may have implications for the optimal outpatient management of these patients that could potentially reduce the rate of hospital admissions of COPD patients suffering from exacerbations.

Patient and exacerbation characteristics for each treatment group may shed light on why many patients did not receive adequate treatment. In our study, patients who did not receive treatment prior to admission (55 %) were those with fewer respiratory symptoms and with a lower incidence of exacerbations. Exacerbations were also milder in this group, with fewer symptoms and a lower frequency of sputum purulence. These differences could, at least partially, explain the lack of treatment administered to these patients, as the lower frequency and milder severity of the exacerbations may lead to the underestimation and underreporting of symptoms. It has been estimated that only 50 % of COPD exacerbations are reported [1], while exacerbation symptoms have been identified by Langsetmo et al. [21] as the strongest predictors of reporting. This is in agreement with the more severe exacerbation symptoms associated with receiving treatment in our study, and supports underreporting as a probable cause for not receiving treatment. Indeed, we found in our study that seeking treatment for acute exacerbations was not common, with only 33 % of patients consulting a general practitioner for a COPD exacerbation, and 22 % treated at least once at emergency departments in the previous year.

Patients in our study received multiple medications for COPD; interestingly, 93.6 % were using inhaled corticosteroids and only 69.1 % were using tiotropium. This pattern is similar to that found in previous surveys in Spain [22] and reflects guidelines for the use of inhaled corticosteroids in severe COPD patients with recurrent exacerbations.

It has been reported that emergency departments are frequently used as an alternative for more rapid outpatient attention [23], and, in our study, the frequency of previous emergency department visits was significantly higher for patients who received treatment versus those who did not. This may be a reflection of treatment-seeking behavior patterns for COPD patients suffering an exacerbation. A study in the hospital setting has shown that, after the onset of exacerbation symptoms, 30 % of patients sought medical attention from a general practitioner or specialist, while the remaining 70 % attended an emergency department [24]. However, this difference in treatment-seeking behavior may reflect patient populations with differing levels of exacerbation severity; of patients with COPD exacerbations attended by general practitioners in the community, only 6 % eventually required hospital admission, while 84 % were prescribed an antibiotic [25].

A recent study by Aaron et al. [26] reported a high incidence (56 %) of exacerbations characterized by sudden onset, where the exacerbation threshold was crossed the same day that the symptoms started. Sudden-onset exacerbations, which would not allow time to seek medical attention, may also explain the large number of patients observed in our study who did not receive treatment before admission. Unfortunately, the onset of symptoms was not an analyzed variable among our patients.

Among the 133 patients treated prior to admission, 43 % did not receive antibiotic therapy, although 93 % fulfilled the criteria for antibiotic treatment according to national guidelines. It is possible that, unlike patients who did not receive prior treatment, this group of patients may have sought medical attention. This raises the possibility that criteria for antibiotic therapy might not be fully recognized among healthcare professionals, or that healthcare professionals are responding to intense pressure to restrict the use of antibiotics, even in severe patients [27]. In addition to the undertreatment of patients eligible for antibiotic therapy, our study also revealed that 10–20 % of patients who did receive antibiotics were not eligible for this therapy according to guidelines [19, 20], supporting the possibility of inappropriate diagnosis and treatment. Additional possibilities such as poor patient adherence to prescriptions must also be considered. Incalzi et al. [18] have reported a similarly low rate of outpatient antibiotic therapy among patients admitted to hospital in Italy, with 80.4 % of patients eligible for antibiotics not receiving them. However, the criteria for antibiotic therapy used by Incalzi et al. differed from ours, as they were based on indices for COPD exacerbation severity, such as age, St. George Respiratory Questionnaire (SGRQ) score, number of exacerbations in the previous year (≥4), and comorbidities.

A total of 25.5 % of our patients received an antibiotic and still required admission to hospital. Several studies have reported an antibiotic failure rate ranging from 12 to 21 % [28, 29], and up to 30 % [30], depending on the severity of the disease and how failure is defined. However, the antibiotic failure rate specific to our study is unknown due to the lack of a control group of patients not needing hospitalization. The reasons for antibiotic therapy failure were not investigated, but a delay in seeking treatment may have added to treatment failures.

The high prevalence of risk factors among our patients may also have contributed to treatment failures; these included FEV1 <35 %, a history of frequent previous exacerbations, ischemic cardiopathy, use of home oxygen, and a high frequency of exacerbations [28, 29], among others. Specific characteristics such as low FEV1, frequent exacerbations, and a high proportion of patients with purulent sputum at baseline suggest that patients in our study may belong to a subgroup of particularly severe patients with COPD who are often colonized [31] and may have bronchiectasis when studied by high-resolution computed tomography (CT) scan [32]. This hypothesis is supported by the fact that patients receiving an antibiotic had a higher frequency of exacerbations in the previous year and a higher prevalence of bronchiectasis compared to treated patients who did not receive an antibiotic. This point is of special relevance, as the presence of bronchiectasis in patients with frequent COPD exacerbations may influence disease management in an effort to prevent bacterial exacerbations [33]. New strategies have been developed with the use of prophylactic antibiotics, either pulsed [34, 35] or with the long-term use of macrolides, as in patients with bronchiectasis not associated to COPD [36, 37]. The development of these new strategies requires the identification and characterization of this particularly severe subgroup of patients who experience frequent hospitalizations [38].

The very low rate of bacterial isolation from sputum in our patients cannot be considered as evidence of the non-bacterial etiology of the exacerbations. The investigation of etiology was not among the study objectives; sputum cultures were only performed in 42 % of patients, with a very low rate of data reporting. Purulence of sputum, although not related directly to the presence of microorganisms but to the activation of granulocytes, is still the best surrogate marker for bacterial infection in the lower airways in COPD [39]. The appropriate use of antimicrobials is crucial in the prevention of the spread of bacterial resistance [40]; however, there are, as yet, no reliable biomarkers for bacterial involvement in exacerbations of COPD [41].

Conclusions

Our results demonstrated a low rate of previous outpatient treatment and of antibiotic use among patients admitted for chronic obstructive pulmonary disease (COPD) exacerbation, despite the fact that the majority of patients fulfilled antibiotic therapy criteria. It is important to highlight the need for educating COPD patients on recognizing symptoms and promptly seeking treatment for exacerbations so that early treatment may prevent hospitalizations. Self-management programs, stressing both aspects of exacerbation management, have been shown to reduce the need for hospitalizations [42, 43], and should be emphasized. Antibiotic treatment for COPD exacerbations according to the criteria set by international and national guidelines should be emphasized among healthcare professionals to obtain the greatest benefit for patients.

Acknowledgments

The authors wish to thank Beatriz Viejo for the editorial support. The following investigators participated in the study: María del Carmen Aguar, Hospital de Vilanova, Valencia (Valencia); Néstor Almeida, Clínica San Roque, Las Palmas de Gran Canaria (Las Palmas); Félix Baranda, Hospital Universitario Cruces, Bilbao (Vizcaya); Marina Blanco, Hospital Universitario A Coruña (A Coruña); Myriam Calle, Hospital Clínico San Carlos, Madrid (Madrid); Francisco Casas, Hospital Clínico San Cecilio, Granada (Granada); José Celdrán, Hospital Nuestra Señora del Prado, Toledo (Toledo); Pedro Cordero, Hospital Nisa 9 de Octubre, Valencia (Valencia); Hugo Dante, Hospital Santa Bárbara, Puertollano (Ciudad Real); David de la Rosa, Clínica Platón, Barcelona (Barcelona); Gustavo de Luiz, Hospital Xanit, Benalmádena (Málaga); Cristobal Esteban, Hospital Galdakao-Usansolo, Galdakao (Vizcaya); Jesús Fernández, Hospital General Universitario de Guadalajara, Guadalajara (Guadalajara); María Ángeles Fernández, Hospital General Río Carrión, Palencia (Palencia); José Vicente Greses, Hospital Nisa 9 de Octubre, Valencia (Valencia); Lourdes Lázaro, Hospital Universitario de Burgos (Burgos); Damián Malía, Hospital General Universitario Los Arcos del Mar Menor, San Javier (Murcia); Pedro Jorge Marcos, Complexo Hospitalario de Ourense (Ourense); Esperanza Martín, Fundació Althaia, Manresa (Barcelona); Luis Molinos, Instituto Nacional de Silicosis, Oviedo (Asturias); Juan Luis Muñoz, Hospital Reina Sofía, Córdoba (Córdoba); Francisco Ortega, Hospital Universitario Virgen del Rocío, Sevilla (Sevilla); Juan Miguel Sánchez, Hospital General Universitario Morales Meseguer, Murcia (Murcia); José Gregorio Soto, Hospital de Jerez, Jerez de la Frontera (Cádiz); Joan Valdeperas, Hospital Universitari de Bellvitge, Barcelona (Barcelona). This work was supported by Bayer Hispania S.L.

Conflict of interest

Marc Miravitlles and Juan José Soler-Cataluña have received speaker fees from Bayer Hispania S.L. Félix Baranda, Pedro Cordero, and José-Vicente Greses declare that they have no conflict of interest. Cristian de la Roza is a full-time employee of Bayer Hispania S.L.

Copyright information

© Springer-Verlag 2012